This is an application for a K08 award for Dr. Charles Chiu, a fellow in adult infectious diseases at the University of California, San Francisco and a 3rd year postdoctoral research fellow with a PhD in biophysics. UCSF is a leading academic biomedical research center with a strong clinical and research community. The work proposed here will help establish the candidate as an independent translational investigator in infectious diseases. The overall goal of the candidate's proposed research is to use an innovative pan-viral DNA microarray (Virochip) to detect and discover viruses associated with human respiratory infection. Acute respiratory tract infection imposes a major economic and health care burden on society. Viruses are associated with both lower and upper respiratory tract illnesses, yet a specific pathogen cannot be identified in 30-60% of cases. The candidate has demonstrated in preliminary experiments that the Virochip is comparable in sensitivity and specificity to that of routine clinical diagnostic tests and that the Virochip is capable of detecting viruses that elude all currently available diagnostic assays. For the proposed research, the candidate will use the Virochip to retrospectively analyze samples of bronchoalveolar lavage fluid from 33 patients with acute respiratory distress syndrome (Aim 1a) and prospectively analyze respiratory secretions from 15-20 critically ill patients in the ICU (Aim 1b) for the presence of viruses. To determine a potential causal relationship between a detected virus and the respiratory illness, the candidate will assess specific antibody responses and look for the virus in other bodily fluids and tissues. To search for novel viruses associated with respiratory illness, the candidate will also use the Virochip to screen culture-negative and viral PCR-negative respiratory samples collected by the California Department of Health Services (Aim 2). The candidate expects that potentially novel viruses will be discovered from this screen, and he will then proceed to sequence and develop specific serological or PCR-based assays for these viruses. Relevance: Understanding viral etiologies of critical respiratory illness may help guide prevention, diagnosis, and treatment of these life-threatening infections. Discovery of a novel respiratory virus would have significant implications on clinical practice and public health and may stimulate development of new antiviral drugs and vaccines.